Vitamin C might complement chemotherapy as a cancer treatment. Very high doses of the vitamin injected into mice attacked tumors and showed signs of working in synergy with chemotherapy drugs. Separately, in a safety trial, 13 women with ovarian cancer given chemotherapy plus high-dose infusions of vitamin C experienced less toxicity from chemo than did women not getting the vitamin.

The idea dates back at least to 1976, when chemist Linus Pauling reported that high doses of intravenous vitamin C given in addition to standard treatment to patients with advanced cancer seemed to increase their survival time. But three years later, Pauling’s findings were countered by a Mayo Clinic study showing that vitamin C taken orally, which resulted in lower levels in the bloodstream, had no effect on cancer patients. While some doctors have continued to use it against cancer, vitamin C fell out of favor and evidence of its effectiveness against cancer is still lacking.

In the new study, researchers implanted mice with ovarian cancer cells and later gave some mice chemotherapy and others chemo plus injected vitamin C. Tumors shrank substantially more in the mice getting the combination, the scientists report in the Feb. 5 Science Translational Medicine.

Vitamin C is an antioxidant that sops up unstable, reactive molecules. But in high doses its role can reverse. The study found that vitamin C killed human ovarian tumor cells in lab dishes by acting as a pro-oxidant, damaging DNA, sabotaging a cellular fuel source called ATP and inhibiting mTOR, a cell growth activator. Healthy ovarian cells were largely unaffected by the high vitamin doses.

Unlike healthy cells, tumor cells may not make the array of proteins necessary to protect themselves from the pro-oxidant assault, says Joseph Cullen, a surgeon at the University of Iowa in Iowa City who wasn’t involved in the study. He also says that tumor cells contain excess iron, which may render them susceptible to high doses of vitamin C.

The researchers also gave intravenous vitamin C to 13 women newly diagnosed with ovarian cancer that had spread to the abdominal cavity. “This reached levels [in the blood] that were 10 to 100 times higher than what is achieved with oral vitamin C,” says study coauthor Qi Chen, a biochemist at the University of Kansas Medical Center in Kansas City. Those women, along with 12 who did not get the vitamin, also received chemotherapy. Over five years, compared with women getting chemo alone, the vitamin C group showed fewer mild or moderate side effects from the chemo, particularly gastrointestinal problems and skin irritation.

Just how vitamin C reduces chemo’s side effects is unclear. Cullen surmises that vitamin C might exert some antioxidant effect that protects healthy tissues even as it delivers pro-oxidant damage to tumor cells.

Patients getting vitamin C infusions went a median of 25.5 months before relapsing; those not getting the vitamin relapsed after 16.75 months. But this difference could be due to chance because of the small numbers of people in the study. Chen and coauthor Jeanne Drisko, a physician and researcher also at Kansas, point out that the study was designed to assess safety, not effectiveness. The findings set the stage for a larger trial of vitamin C, Drisko argues. “It’s safe, inexpensive and seems to be working hand in hand with chemotherapy,” she says.